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Biomedical subjects

A Reviczky

Publications and source records attributed to A Reviczky.

At least 19 recordsLinked to original sources
PubMed1994

Metabolism of sulfoconjugated thyroid hormone derivatives in developing sheep.

Although the production of thyroxine (T4) in the developing ovine fetus ranges from 20 to 50 micrograms.kg-1.day-1, production rates for 3,5,3'-triiodothyronine (T3) average only 1-2 micrograms.kg-1.day-1, whereas reverse T3 (rT3) production rates approach 5-6 micrograms.kg-1.day-1. Thus the fate of the majority of fetal T4 production is uncertain. Recently we have reported significant concentrations of various thyroid hormone sulfoconjugates in serum and other fetal compartments. In the present study, we used steady-state kinetic techniques in developing sheep to establish the clearance and production rates for T4, T3, and rT3 sulfates. These studies confirm that T4, T3, and rT3 sulfate are predominant metabolites of thyroid hormone in the developing ovine fetus. Plasma clearance rates for T3, T4, and rT3 sulfates are low in the fetus, averaging 0.67 +/- 0.07, 1.46 +/- 0.11, and 4.1 +/- 1 ml.kg-1.min-1, respectively. Clearance rates for these thyrosulfoconjugates increase two to fourfold postnatally, probably reflecting increased activity of 5'-monodeiodinase after birth. Moreover, fetal production rates for these sulfated thyroid hormone metabolites exceed those of 2-wk-old sheep 4- to 10-fold. The data suggest that a significant route of fetal T4 metabolism is sulfation followed by deiodination to rT3 sulfate.

Aging↗
PubMed1993

Sulfate conjugates of iodothyronines in developing sheep: effect of fetal hypothyroidism.

We recently showed that thyroxine sulfate (T4S) and 3,3',5-triiodothyronine sulfate (T3S) were major thyroid hormone metabolites in ovine fetuses and neonates. To further characterize the sulfation pathway in ovine fetuses, we measured 3,3',5'-triiodothyronine (rT3S) in serum and other body fluids in samples obtained from fetal (n = 23, 94-145 days of gestational age, term = 150 days), newborn (n = 6), and adult (n = 6) sheep. In addition, T3S, T4S, and rT3S levels were measured in tissue fluids and serum samples obtained from ovine fetuses 13 days after total thyroidectomy (Tx) conducted at gestational age of 110-113 days (n = 5). Sham-operated twin fetuses served as controls (n = 5). The relative order of mean rT3S concentration for various tissue fluids in fetuses were meconium > bile > serum > allantoic fluid > urine or amniotic fluid. Peak mean tissue fluid levels generally occurred at 110-130 days gestation. In hypothyroid fetuses, significant decreases in the mean serum concentrations of T4S and rT3S, but not T3S, were noted. The mean rT3S level also was decreased significantly in allantoic fluid, bile, and meconium, whereas T4S and T3S levels were reduced only in bile of the Tx fetuses. These data demonstrate that sulfation is a major pathway in thyroid hormone metabolism in both euthyroid and hypothyroid ovine fetuses.

Animals↗
PubMed1993

The development of a radioimmunoassay for reverse triiodothyronine sulfate in human serum and amniotic fluid.

Sulfated iodothyronines including T4-sulfate (T4S) and T3-sulfate (T3S) have been identified in human serum and amniotic fluid. Little is known, however, about the existence of sulfate conjugation of reverse T3 (rT3S) in man. In this report, we employed a novel, sensitive, and specific rT3S RIA to address this question. The rabbit antiserum to rT3S was highly specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reaction with the antiserum. Only T4S and T3S cross-reacted significantly (0.3% and 0.01%, respectively); other analogs cross-reacted less than 0.0001%. The detection threshold of the RIA was 14 pmol/L (1.0 ng/dL). The mean serum rT3S concentration (pmol/L) was 40 in euthyroid subjects. Values were similar in hypothyroid patients (38) and pregnant women (52) but significantly (P < 0.01) elevated to 176 in hyperthyroid patient, 74 in patients with nonthyroid illnesses, and 684 in cord sera of newborns. Serum rT3S increased significantly in hyperthyroid patients 1 day after administration of 1 g sodium ipodate orally. Reverse T3S was detected consistently in amniotic fluid at 14 to 22 weeks of gestation and showed a marked rise 1-3 weeks after intraamniotic administration of 500-1000 micrograms T4. The various data suggest that: (1) rT3S is a normal component of human serum and amniotic fluid; (2) it is derived from metabolism of T4 or rT3; (3) circulating rT3S increases in hyperthyroidism and in circumstances where type I 5'-monodeiodinating activity is low, e.g. nonthyroid illnesses, fetal life, and after administration of ipodate.

Amniotic Fluid↗
PubMed1992

Ontogeny of epidermal growth factor, transforming growth factor-alpha, epidermal growth factor receptor, and thyroid hormone receptor RNA levels in rat kidney and changes in those levels induced by early thyroxine treatment.

Ontogenic changes in the mRNA levels of epidermal growth factor (EGF), transforming growth factor-alpha, EGF receptor, and thyroid hormone receptor (r-erbA) were examined in developing rat kidneys. The mRNA levels of both EGF and thyroid hormone receptor rose dramatically during the postnatal period with the rise in thyroid hormone receptor message preceding the rise in EGF message. In addition, we examined renal mRNA levels in 1-wk-old rats treated with thyroxine (T4) from birth through d 6. Neonatal T4 treatment augmented the renal mRNA levels of EGF but decreased the levels of EGF-receptor and transforming growth factor-alpha. T4 treatment did not significantly affect the levels of renal mRNA for thyroid hormone receptor. Although the EGF and transforming growth factor-alpha peptides are similar and interact with the same receptor, our findings indicate that these homologous growth factors are regulated differently during development. In addition, hormones that influence growth and development, such as T4, may function both as positive and negative regulators of growth factor expression.

Age Factors↗
PubMed1992

Thyroxine sulfate is a major thyroid hormone metabolite and a potential intermediate in the monodeiodination pathways in fetal sheep.

T3 and rT3 production rates in the fetus account for roughly only a third of the total T4 production rate; thus, the fate of the majority of T4 produced in the fetus is unknown (the "T4 disposal gap"). We developed sensitive and specific T4 sulfate (T4S) and T3 sulfate (T3S) RIAs to investigate the roles of these compounds in fetal T4 metabolism. T3, T4, T3S, and T4S were determined in a variety of tissue fluid and/or serum samples obtained from fetal, newborn (n = 6), and adult (n = 6) sheep. Four groups of fetal animals, with gestational ages of 94 days (n = 5), 110-111 days (n = 6), 130-131 days (n = 6), and 145 days (n = 6; term = 150 days), were studied. In addition, type I 5'-monodeiodinase (5'-MDI) activity was quantified in liver and kidney tissues. 5'-MDI activities were lower in 94- to 131-day-old fetuses than in fetuses near term or in newborn animals. Mean serum T3 concentrations increased progressively from 94 days (19 ng/dl) to term (371 ng/dl), while mean T3S and T4S serum concentrations were highest at 130 days gestation (237 and 989 ng/dl), decreasing to term. Serum T3S and T4S concentrations decreased further in newborns and adult sheep. T4S and T3S levels in allantoic fluid were significantly higher than those in urine and amniotic fluid in all fetal age groups studied. T4S levels in bile were high from 94-130 days gestation (873-1006 ng/dl), decreasing by 50% at term (529 ng/dl). T4S concentrations in meconium were 46- to 83-fold higher than those in bile from 94 days gestation to term. In contrast, bile T3S levels increased progressively from 94-145 days gestation (191-605 ng/dl), while meconium T3S levels decreased during the same period (33-14 micrograms/100 g). These data demonstrate that 1) sulfated iodothyronines, particularly T4S, are major thyroid hormone metabolites in the fetus; 2) both T4S and T3S are excreted into bile and urine and concentrated in meconium and allantoic fluid; and 3) the high levels of T4S and T3S in serum and other fluids may reflect lower tissue type I 5'-MDI activities. We speculate that T4S and T3S may be further metabolized to other sulfated metabolites and may account in part for the T4 disposal gap in fetal sheep.

Allantois↗
PubMed1991

Thyrotropin-releasing hormone in ovine fetus: ontogeny and effect of thyroid hormone.

The ontogenesis of hypothalamic and extrahypothalamic thyrotropin-releasing hormone (TRH) and the effect of altered thyroid status on tissue TRH levels were studied in fetal sheep. At 62 days gestation (term = 145 days) TRH was detectable in serum and in hypothalamic, placental, and pancreatic tissues; pancreatic, placental, and serum levels exceeded hypothalamic levels two- to fivefold. Analysis of tissues obtained from 88-day gestation fetuses were comparable: TRH levels in placenta (54 +/- 15 pg/mg tissue protein), pancreas (34 +/- 5 pg/mg protein), and serum (93 +/- 9 pg/ml) exceeded those in hypothalamic extracts (15 +/- 9 pg/mg protein). By 120 days gestation, TRH values in the hypothalamus (610 +/- 52 pg/mg protein) exceeded those in extrahypothalamic sites; values were comparable at 140 days gestation. Fetal thyroidectomy resulted in a 2-fold elevation of hypothalamic TRH concentrations (1,030 +/- 139 vs. 522 +/- 29 pg/mg protein) and 2 to 20-fold elevations of TRH in the placenta (147 +/- 23 vs. 42 +/- 8 pg/mg protein), pancreas (195 +/- 11 vs. 29 +/- 7 pg/mg protein), duodenum (363 +/- 97 vs. 29 +/- 7 pg/mg protein), and serum (2,563 +/- 212 vs. 131 +/- 16 pg/ml). 3, 5, 3'-Triiodothyronine (T3) infusion in thyroidectomized fetuses resulted in elevated serum T3 values (480 +/- 80 ng/dl) and suppressed hypothalamic TRH (249 +/- 68 vs. 522 +/- 29 pg/mg protein) and serum TRH concentrations (30 +/- 4 vs. 131 +/- 156 pg/ml). Placental, pancreatic, and duodenal TRH concentrations in thyroidectomized T3-infused animals were below the level of detection of the assay (5 pg/mg tissue protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Nuclear thyroid hormone receptors: ontogeny and thyroid hormone effects in sheep.

To investigate the mechanism(s) responsible for the paucity of fetal thyroid hormone effects, thyroid hormone nuclear receptor (T3NR) binding characteristics were quantified in liver and brain of fetal and neonatal sheep. Maximal binding capacities [MBC; mean +/- SE fmol 3,5,3'-triiodothyronine (T3)/mg DNA] in liver increased from values of 68 +/- 14 at 80 days gestation to 684 +/- 152 at term. Liver T3NR MBC in newborn and adult sheep were comparable to values in term fetuses. Liver T3NR binding affinities were similar in all animals, averaging 1.68 +/- 0.05 X 10(9) M-1. Brain T3NR MBC were comparable at all fetal ages studied (410 +/- 55 fmol T3/mg DNA), increasing to 1,517 +/- 315 fmol T3/mg DNA during the 1st postnatal week and returning to comparable fetal values (368 +/- 37 fmol T3/mg DNA) in the 3rd week after birth. Brain T3NR binding affinities were comparable in all animals studied (7.5 +/- 2.1 X 10(9) M-1), and the mean value was significantly greater than mean liver T3NR affinity. T3NR binding of T3 analogues in six term fetal animals were qualitatively similar for both brain and liver and showed T3 = triiodothyroacetic acid greater than thyroxine greater than reverse T3. Like T3 binding affinity, T3NR analogue binding affinities in brain tissue were five- to sevenfold greater than those in liver. Fetal hypothyroidism induced by thyroidectomy at either 99-107 or 129-132 days of gestation was not associated with changes in brain or liver T3NR binding characteristics. The heterogenous ontogeny and binding characteristics of brain and liver T3NR is compatible with the hypothesis that different thyroid hormone receptors are expressed in these tissues.

Animals↗
PubMed1987

Effect of fetal thyroidectomy on newborn thermogenesis in lambs.

We investigated the effect of the transient neonatal hyperthyroid state on thermogenesis at birth by measuring rectal temperature, plasma free fatty acids, plasma catecholamines, and in vitro brown adipose tissue respiration in thyroidectomized (n = 6) and sham operated (n = 5) fetal sheep. Surgery was performed at an average of 133 days of gestation followed by cesarean delivery at 146 days. Fetuses were delivered into a constant room temperature of 25 degrees C. Serial measurements were made in utero before delivery and at timed intervals after birth. Serum 3,3',5 triiodothyronine and thyroxine concentrations in the neonatal period were normal in sham operated and nondetectable in thyroidectomized fetuses. Rectal temperatures and serum free fatty acid levels were reduced in thyroidectomized newborns. Plasma epinephrine concentrations were increased and the hypothyroid neonates were acidotic when compared to control animals. In vitro basal and norepinephrine stimulated brown adipose tissue respiration were reduced in thyroidectomized compared to control animals. These results indicate that thyroid hormone deficiency impairs nonshivering thermogenesis in brown adipose tissue and leads to hypothermia despite augmented plasma epinephrine values.

Adipose Tissue, Brown↗
PubMed1984

Thyroid hormones augment catecholamine-stimulated brown adipose tissue thermogenesis in the ovine fetus.

The effects of exogenous changes in thyroid status on in vitro brown adipose tissue (BAT) cellular respiration and thermogenic enzymes (sodium-potassium ATP' ase and alpha-glycerophosphate dehydrogenase) were studied in fetal sheep. Thyroidectomy and insertion of a constant infusion pump followed by 8 days of infusion of either T3 (n = 7) or vehicle (n = 4) were performed in fetal lambs at 119-121 days gestation. The animals were then killed, and perirenal BAT was removed for study. T3 infusion resulted in a mean plasma T3 concentration of 322 +/- 52 ng/dl compared to levels at the limits of detection (9 ng/dl) in the vehicle-infused animals. Basal respiration values with or without ouabain were similar in the two groups. Maximum mean norepinephrine (NE; 10(-6) M)-stimulated respiration (110.2 +/- 11.6 microliter O2/10(6) cells X h) in the T3-treated group was greater than stimulated mean respiration (55.3 +/- 15.6 microliter O2/10(6) cells X h) in the untreated animals (P less than 0.02). NE-stimulated respiration in the presence of ouabain (i.e. nonsodium transport-dependent respiration) was increased in the T3-treated animals (P less than 0.01), while sodium transport-dependent respiration was not different. (Bu)2cAMP-stimulated respiration was greater in the T3-treated group (P less than 0.001), while alpha-glycerophosphate substrate respiration was not different. Mitochondrial alpha-glycerophosphate dehydrogenase and Na-K-ATPase activities were similar. These studies demonstrate that BAT catecholamine-stimulated respiration is influenced by thyroid status in the ovine fetus. The increase in both NE- and (Bu)2cAMP-stimulated respiration suggests a postreceptor effect on intracellular metabolism, though an effect on beta-adrenergic receptors also might have occurred. Neither sodium transport (NA-K-ATPase)-dependent respiration nor mitochondrial alpha-glycerophosphate dehydrogenase appear to be involved. These data suggest that the relative hyperthyroid state that occurs in the newborn of both man and sheep may be important through its effects on BAT metabolism to insure adequate temperature regulation during neonatal adaptation.

Adipose Tissue, Brown↗
PubMed1983

Effect of changes in thyroid status on tissue respiration in fetal and newborn sheep.

The effect of both exogenous and endogenous changes in thyroid status on in vitro tissue respiration and thermogenic enzymes (sodium-potassium-adenosine triphosphatase and alpha-glycerophosphate dehydrogenase) was studied in fetal and newborn sheep. Oxygen consumption of liver and brain increased from 25 +/- 4.1 and 58.5 +/- 2.8 microliters O2 X 100 mg-1 X h-1, respectively, in tissues from unthyroidectomized fetal animals at 136-140 days gestation to 60 +/- 4.2 and 72 +/- 1.5 microliters O2 X 100 mg-1 X h-1 in tissues from unthyroidectomized newborn lambs between birth and 7 days of age. The physiological changes in thyroid function that normally occur at birth resulted in a mean (+/- SE) plasma triiodothyronine (T3) concentration of 563 +/- 39 ng/dl in the newborn lambs compared with 39 +/- 8 ng/dl in the fetal animals. Kidney respiration and thermogenic enzyme activities in the several tissues studied did not change. Liver, kidney, and brain respiration and thermogenic enzymes from T3-treated thyroidectomized fetal and newborn lambs were not increased (compared with untreated thyroidectomized animals) despite a marked increase in plasma T3 concentrations. Conclusions are that 1) liver, kidney cortex, and frontal brain cortex in the fetal and newborn lamb are relatively insensitive to the calorigenic effect of thyroid hormones, and 2) a perinatal increase in hepatic and cerebral respiration occurs in newborn animals (compared with fetal animals) but is probably not due solely to perinatal increases in thyroid hormones.

Animals↗
PubMed1983

Development of brown adipose tissue thermogenesis in the ovine fetus and newborn.

Despite the importance of brown adipose tissue (BAT) in the regulation of thermogenesis and energy expenditure in both newborn and adult mammals, the functional ontogenesis of this tissue is largely unknown. In the present study, we describe the maturation of several aspects of BAT thermogenesis in fetal and newborn sheep. Cell respiration of brown adipocytes isolated from perirenal BAT was measured using a Gilson differential respirometer. Cells were isolated from four fetal animals at 121-124 days gestation (group 1), five fetal animals at 137-140 days gestation (group 2), and five newborns between birth and 4 days of age (group 3). In addition to basal oxygen consumption, in vitro cell respiration also was measured after the addition of norepinephrine (NE), (Bu)2cAMP, alpha-glycerophosphate (alpha GP), and butyric acid. Mean (+/- SEM) basal respiration (in microliters of O2 per 10(6) cells/h) increased from 11 +/- 1 in group 1 to 31 +/- 2 in group 2 and 45 +/- 7 in group 3. Cell volume increased from 9 +/- 1 pl in group 1 to 13 +/- 2 pl in group 2 and 18 +/- 2 pl in group 3. After adjustment for variations in basal respiration due to differences in cell volume, basal respiration in group 2 was greater than that in group 1 and equal to that in group 3. Maximal NE (10(-6) M)-stimulated respiration increased from 74 +/- 16 in group 1 to 294 +/- 47 in group 2. Maximal NE-stimulated respiration in group 3 (133 +/- 30) was less than that in group 2, but equal to that in group 1. (Bu)2cAMP-stimulated respiration increased from 51 +/- 12 in group 1 to 175 +/- 22 in group II, with no further increase in group III. Neither NE- nor (Bu)2cAMP-stimulated respiration varied significantly with cell volume. alpha GP substrate respiration demonstrated significant increases from group 1 to group 2, with another significant increase in Group 3. Butyric acid substrate respiration in group 1 was less than those measured in groups 2 and 3, while respiration values in groups 2 and 3 were equal. After adjustments for variations due to differences in cell volume, the patterns of development of both alpha GP and butyric acid substrate respiration were unaltered. The following conclusions were reached 1) Full maturation of BAT catecholamine-stimulated cellular respiration occurs before delivery near term in the ovine fetus. 2) In the neonatal lamb, a decrease in catecholamine-stimulated respiration occurs without a decrease in (Bu)2cAMP-stimulated respiration. This suggests that a decrease in BAT sensitivity to NE occurs after delivery at the receptor adenyl cyclase level. 3) The perinatal increase in alpha GP substrate respiration without an increase in butyric acid substrate respiration suggests that mitochondrial alpha-glycerophosphate dehydrogenase activity is increased. This was confirmed by measuring increased alpha-glycerophosphate dehydrogenase activity in crude BAT mitochondrial fractions in group 3 animals.

Adipose Tissue, Brown↗
PubMed1981

Thyroid hormone-sensitive brown adipose tissue respiration in the newborn rabbit.

The effects of thyroid hormone treatment on brown adipose tissue (BAT) and liver metabolism were assessed by measuring oxygen consumption, sodium-potassium adenosine triphosphatase (Na-K-ATPase), and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activities in tissues from triiodothyronine- (T3) and vehicle-injected (for 3 days) newborn and adult rabbits. In the newborns, basal BAT cellular respiration was increased [mean (%/- SE) = 119 +/- 18 vs. 65 +/- 4 microliter O2/10(6) cells-1 . h in controls (P less than 0.005)], whereas hepatic respiration was unchanged. Ouabain had no effect on basal BAT cellular respiration, but suppressed hepatic respiration by 30% in both newborn groups. T3 treatment had no effect on NE- (10(-6) M) stimulated BAT respiration, whereas adult hepatic respiration was increased almost twofold. alpha-GPD activities were increased in both newborn BAT and adult liver but not in newborn liver. Na-K-ATPase activity was significantly increased only in newborn liver. In conclusion, 1) both BAT and liver are thyroid-hormone sensitive in the newborn rabbit, but the responses to T3 treatment are different in the two tissues; 2) the failure to stimulate both hepatic alpha-GPD and respiration in the newborn appears to be a developmental phenomenon characteristic of the rabbit; 3) thyroid hormones have little effect on sodium transport-dependent respiration in either BAT of liver in the newborn rabbit.

Adipose Tissue, Brown↗
PubMed1980

Effect of osmolality on arginine vasopressin and renin release after hemorrhage.

The effects of alterations of plasma osmolality on plasma arginine vasopressin (AVP) and renin activity (PRA) following graded hemorrhage were studied in conscious dogs who were either euhydrated, dehydrated, water loaded, or infused with hypertonic saline. Base-line plasma osmolality and AVP were significantly different in the four treatment groups; however, following hemorrhage the increases in log AVP did not significantly differ. An unexpected finding was that water loading resulted in significant elevations in PRA and plasma aldosterone concentrations, whereas plasma osmolality and AVP were reduced. Prior to hemorrhage, PRA was significantly greater in the water-loaded and dehydrated groups than in the euhydrated or saline-infused groups; following hemorrhage the increases in log PRA were not significantly different in all four treatment groups. The data suggest that, although alterations in osmolality influence base-line levels of AVP, they have no effect on relative (logarithmic) rises in AVP following hemorrhage. Similarly, alterations in AVP may influence base-line PRA, but do not influence relative rises in PRA following hemorrhage.

Animals↗
PubMed1979

Hemoglobin Lepore Washington and hemochromatosis in a Hungarian patient.

A Hungarian family with four heterozygotes for Hb Lepore Washington is described. One, a 43-year-old male, had high levels of serum iron, saturated iron-binding capacity, and ferritin, and normal levels of folic acid and vitamin B12. Liver biopsy showed slight cirrhosis and marked iron deposition in parenchymal cells and in cells of the reticuloendothelial system. Heavy iron deposition was also found in the bone marrow. The patient is not an alcoholic and has no disease that requires blood transfusion. The hemochromatosis thus seems to be of idiopathic nature.

Adolescent↗
PubMed1977

A critical analysis of some thyroid function tests.

The results of a comparative study of thyroid function tests are reported, the assay for PBI having been used for reference. The merits and sources of error of the Bio-Rad column test, Thyopac-4 test and T3-RIA test are discussed with reference to PBI. The correlation coefficients and the sources of error being taken into consideration, PBI represents a fairly reliable indicator of T4 values and recommends itself on these grounds as a basic routine procedure, the more so as it is simple, cheap and suited for automated analysis. In case of iodine contamination or of the necessity for a selective identification of the T4 factor, the T4 column test is equally reliable. The T3-RIA test will be valuable in special diagnostic problems.

Humans↗